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Article ; Online: Complexities in Predicting the Immunogenicity of Live Attenuated Influenza Vaccines.

Lindsey, Benjamin B / Höschler, Katja / de Silva, Thushan I

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2019 Volume 70, Issue 10, Page(s) 2235–2236

MeSH term(s)	Humans ; Influenza Vaccines ; Influenza, Human/prevention & control ; Vaccines, Attenuated
Chemical Substances	Influenza Vaccines ; Vaccines, Attenuated
Language	English
Publishing date	2019-08-26
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciz773
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Article ; Online: Health-seeking behaviour and beliefs around sore throat in The Gambia: A qualitative study.

Suau Sans, Maria / Manneh, Muhammed / Ceesay, Isatou / Bittaye, Amat / de Crombrugghe, Gabrielle / Keeley, Alexander J / de Silva, Thushan I / Palmer, Jennifer / Armitage, Edwin P / Marks, Michael

PLOS global public health

2024 Volume 4, Issue 3, Page(s) e0002257

Abstract: Group A Streptococcus (Strep A) bacteria causes a broad spectrum of diseases. The most common manifestations of Strep A infection are sore throat and pus-producing skin infections such as impetigo. Complications of Strep A infection can lead to ... ...

Abstract	Group A Streptococcus (Strep A) bacteria causes a broad spectrum of diseases. The most common manifestations of Strep A infection are sore throat and pus-producing skin infections such as impetigo. Complications of Strep A infection can lead to inflammation in the bones, muscles, joints, and internal organs causing acute rheumatic fever and rheumatic heart disease (RHD). In The Gambia, the RHD burden is thought to be very high. However, epidemiological data is minimal, and Strep A control programmes do not exist. This study aimed to explore common beliefs and practices related to sore throats among primary caregivers of children, and healthcare providers in a community with a high Strep A disease burden. Four informal conversations with providers and fifteen semi-structured interviews with caregivers were conducted in the peri-urban area of Sukuta, The Gambia. Sampling was purposive and gradual, beginning from households identified to have recently experienced sore throat through a parallel cohort study. Themes explored in qualitative analysis included: sore throat causal attributions and diagnoses, care practises, health-seeking behaviour, and perceived barriers to using the biomedical sector. We found that sore throats were typically perceived to affect one child in a family, disproportionately or exclusively. Sore throats were rarely perceived as life-threatening, and awareness of links between sore throat and ARF or RHD was not reported among caregivers or providers in this study population. Most cases of sore throat were initially managed at home using traditional medicine which delayed resort to antibiotics, though in two instances of severe pain with the presence of exudate, fear that the child's life was at risk prompted care-seeking through the formal health system. Our findings can inform the development of tailored strategies to increase community knowledge of the potential long-term consequences of sore throats and appropriate care-seeking, alongside improvements in the health system, to prevent Strep A sequelae effectively.
Language	English
Publishing date	2024-03-25
Publishing country	United States
Document type	Journal Article
ISSN	2767-3375
ISSN (online)	2767-3375
DOI	10.1371/journal.pgph.0002257
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Article ; Online: Development and characterization of a hemolysis inhibition assay to determine functionality of anti-Streptolysin O antibodies in human sera.

Carducci, Martina / Whitcombe, Alana / Rovetini, Luca / Massai, Luisa / Keeley, Alexander J / de Silva, Thushan I / Bennett, Julie / Berlanda Scorza, Francesco / Iturriza, Miren / Moreland, Nicole J / Moriel, Danilo G / Rossi, Omar

Journal of immunological methods

2024 Volume 526, Page(s) 113618

Abstract: The high burden of disease and the long-lasting sequelae following Streptococcus pyogenes (Strep A) infections make the development of an effective vaccine a global health priority. Streptolysin O (SLO), is a key toxin in the complex pathogenesis of ... ...

Abstract	The high burden of disease and the long-lasting sequelae following Streptococcus pyogenes (Strep A) infections make the development of an effective vaccine a global health priority. Streptolysin O (SLO), is a key toxin in the complex pathogenesis of Strep A infection. Antibodies are elicited against SLO after natural exposure and represent a key target for vaccine-induced immunity. Here we present the setup and characterization of a hemolysis assay to measure functionality of anti-SLO antibodies in human sera. Assay specificity, precision, linearity, reproducibility, and repeatability were determined. The assay was demonstrated to be highly sensitive, specific, reproducible, linear and performed well in assessing functionality of anti-SLO antibodies induced by exposed individuals. Moreover, different sources of critical reagents, in particular red- blood cells, have been compared and had minimal impact on assay performance. The assay presented here has throughput suitable for evaluating sera in vaccine clinical trials and sero-epidemiological studies to gain further insights into the functionality of infection- and vaccine-induced antibodies.
MeSH term(s)	Humans ; Streptococcus pyogenes ; Hemolysis ; Reproducibility of Results ; Streptolysins/pharmacology ; Bacterial Proteins ; Antibodies/pharmacology ; Streptococcal Infections/diagnosis ; Vaccines
Chemical Substances	Streptolysins ; Bacterial Proteins ; Antibodies ; Vaccines
Language	English
Publishing date	2024-01-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120142-6
ISSN	1872-7905 ; 0022-1759
ISSN (online)	1872-7905
ISSN	0022-1759
DOI	10.1016/j.jim.2024.113618
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Article ; Online: Asymptomatic SARS-CoV-2 infection: the tip or the iceberg?

Keeley, Alexander J / Evans, Cariad M / de Silva, Thushan I

Thorax

2020 Volume 75, Issue 8, Page(s) 621–622

MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS Virus ; SARS-CoV-2 ; Washington
Keywords	covid19
Language	English
Publishing date	2020-06-24
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thoraxjnl-2020-215337
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Article ; Online: Potential impact of influenza vaccine roll-out on antibiotic use in Africa.

Knight, Gwenan M / Clarkson, Madeleine / de Silva, Thushan I

The Journal of antimicrobial chemotherapy

2018 Volume 73, Issue 8, Page(s) 2197–2200

Abstract: Background: Influenza infections result in both inappropriate and appropriate antibiotic prescribing. There is a huge burden of both influenza and infections caused by antimicrobial-resistant pathogens in Africa. Influenza vaccines have the potential to ...

Abstract	Background: Influenza infections result in both inappropriate and appropriate antibiotic prescribing. There is a huge burden of both influenza and infections caused by antimicrobial-resistant pathogens in Africa. Influenza vaccines have the potential to reduce appropriate antibiotic use, through reduction of secondary bacterial infections, as well as to reduce levels of influenza misdiagnosed and treated as a bacterial infection (inappropriate). Objectives: To estimate potential reductions in antibiotic use that are achievable by introducing an influenza vaccine into various African settings. Methods: Influenza incidence was combined with population size, vaccine and health system characteristics. Results: We estimated that the direct impact of vaccination could avert more than 390 prescriptions per 100 000 population per year if a 50% efficacious influenza vaccine at 30% coverage was introduced to adults >65 years old in South Africa or children 2-5 years old in Senegal. Across Africa, purely through reducing the number of severe acute respiratory infections, the same vaccine characteristics could avert at least 24 000 antibiotic prescriptions per year if given to children <5 years old. Conclusions: The introduction of an influenza vaccine into multiple African settings could have a dramatic indirect impact on antibiotic usage. Our values are limited underestimates, capturing only the direct impact of vaccination in a few settings and risk groups. This is owing to the huge lack of epidemiological information on antibiotic use and influenza in Africa. However, it is likely that influenza vaccination in Africa could substantially impact antibiotic usage in addition to influenza-related mortality and morbidity.
MeSH term(s)	Africa/epidemiology ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Child, Preschool ; Drug Utilization/statistics & numerical data ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Influenza Vaccines/administration & dosage ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Male ; Pregnancy
Chemical Substances	Anti-Bacterial Agents ; Influenza Vaccines
Language	English
Publishing date	2018-05-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dky172
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Zs.MO 124: Show issues

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Article ; Online: Development and Characterisation of a Four-Plex Assay to Measure

Keeley, Alexander J / Carducci, Martina / Massai, Luisa / Pizza, Mariagrazia / de Silva, Thushan I / G Moriel, Danilo / Rossi, Omar

Methods and protocols

2022 Volume 5, Issue 4

Abstract: The measurement of antibodies to vaccine antigens is crucial for research towards a safe and effective vaccine ... ...

Abstract	The measurement of antibodies to vaccine antigens is crucial for research towards a safe and effective vaccine for
Language	English
Publishing date	2022-06-27
Publishing country	Switzerland
Document type	Journal Article
ISSN	2409-9279
ISSN (online)	2409-9279
DOI	10.3390/mps5040055
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Article ; Online: Value of immunogenicity studies of influenza vaccine in resource-limited settings.

de Silva, Thushan I / Kampmann, Beate

The Lancet. Global health

2017 Volume 5, Issue 3, Page(s) e274

MeSH term(s)	Health Resources ; Humans ; Influenza Vaccines ; Vaccination ; Vaccines, Inactivated
Chemical Substances	Influenza Vaccines ; Vaccines, Inactivated
Language	English
Publishing date	2017-01-22
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	2723488-5
ISSN	2214-109X ; 2214-109X
ISSN (online)	2214-109X
ISSN	2214-109X
DOI	10.1016/S2214-109X(17)30038-4
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Article ; Online: SARS-CoV-2 variant biology: immune escape, transmission and fitness.

Carabelli, Alessandro M / Peacock, Thomas P / Thorne, Lucy G / Harvey, William T / Hughes, Joseph / Peacock, Sharon J / Barclay, Wendy S / de Silva, Thushan I / Towers, Greg J / Robertson, David L

Nature reviews. Microbiology

2023 Volume 21, Issue 3, Page(s) 162–177

Abstract: In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited a major step change in its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates ...

Abstract	In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited a major step change in its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates of transmission relative to previous variants and were termed 'variants of concern' (VOCs). Designated Alpha, Beta, Gamma, Delta and Omicron, the VOCs emerged independently from one another, and in turn each rapidly became dominant, regionally or globally, outcompeting previous variants. The success of each VOC relative to the previously dominant variant was enabled by altered intrinsic functional properties of the virus and, to various degrees, changes to virus antigenicity conferring the ability to evade a primed immune response. The increased virus fitness associated with VOCs is the result of a complex interplay of virus biology in the context of changing human immunity due to both vaccination and prior infection. In this Review, we summarize the literature on the relative transmissibility and antigenicity of SARS-CoV-2 variants, the role of mutations at the furin spike cleavage site and of non-spike proteins, the potential importance of recombination to virus success, and SARS-CoV-2 evolution in the context of T cells, innate immunity and population immunity. SARS-CoV-2 shows a complicated relationship among virus antigenicity, transmission and virulence, which has unpredictable implications for the future trajectory and disease burden of COVID-19.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; COVID-19 ; Immunity, Innate ; Biology
Language	English
Publishing date	2023-01-18
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2139054-X
ISSN	1740-1534 ; 1740-1526
ISSN (online)	1740-1534
ISSN	1740-1526
DOI	10.1038/s41579-022-00841-7
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Article ; Online: Acquisition and carriage of genetically diverse multi-drug resistant gram-negative bacilli in hospitalised newborns in The Gambia.

Bah, Saikou Y / Kujabi, Mariama A / Darboe, Saffiatou / Kebbeh, Ngange / Kebbeh, Bunja F K / Kanteh, Abdoulie / Bojang, Ramatouille / Lawn, Joy E / Kampmann, Beate / Sesay, Abdul K / de Silva, Thushan I / Brotherton, Helen

Communications medicine

2023 Volume 3, Issue 1, Page(s) 79

Abstract: Background: This detailed genomic study characterised multi-drug resistant-Gram negative bacilli (MDR-GNB) carriage in neonates < 2 kg and paired mothers at a low-resource African hospital.: Methods: This cross-sectional cohort study was conducted at ...

Abstract	Background: This detailed genomic study characterised multi-drug resistant-Gram negative bacilli (MDR-GNB) carriage in neonates < 2 kg and paired mothers at a low-resource African hospital. Methods: This cross-sectional cohort study was conducted at the neonatal referral unit in The Gambia with weekly neonatal skin and peri-anal sampling and paired maternal recto-vaginal swabs. Prospective bacteriological culture used MacConkey agar with species identification by API20E and API20NE. All GNB isolates underwent whole genome sequencing on Illumina Miseq platform. Multi-Locus Sequence Typing and SNP-distance analysis identified strain type and relatedness. Results: 135 swabs from 34 neonates and 21 paired mothers, yielded 137 GNB isolates, of which 112 are high quality de novo assemblies. Neonatal MDR-GNB carriage prevalence is 41% (14/34) at admission with 85% (11/13) new acquisition by 7d. Multiple MDR and ESBL-GNB species are carried at different timepoints, most frequently K. pneumoniae and E. coli, with heterogeneous strain diversity and no evidence of clonality. 111 distinct antibiotic resistance genes are mostly beta lactamases (Bla-AMPH, Bla-PBP, CTX-M-15, Bla-TEM-105). 76% (16/21) and 62% (13/21) of mothers have recto-vaginal carriage of ≥1 MDR-GNB and ESBL-GNB respectively, mostly MDR-E. coli (76%, 16/21) and MDR-K. pneumoniae (24%, 5/21). Of 21 newborn-mother dyads, only one have genetically identical isolates (E. coli ST131 and K. pneumoniae ST3476). Conclusions: Gambian hospitalised neonates exhibit high MDR and ESBL-GNB carriage prevalence with acquisition between birth and 7d with limited evidence supporting mother to neonate transmission. Genomic studies in similar settings are required to further understand transmission and inform targeted surveillance and infection prevention policies.
Language	English
Publishing date	2023-06-03
Publishing country	England
Document type	Journal Article
ISSN	2730-664X
ISSN (online)	2730-664X
DOI	10.1038/s43856-023-00309-6
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Article ; Online: Efficient overexpression and purification of SARS-CoV-2 Nucleocapsid proteins in Escherichia coli

Brudenell, Emma L / Pohare, Manoj B / Zafred, Domen / Phipps, Janine / Hornsby, Hailey R / Darby, John / Dai, Junxiao / Liggett, Ellen / Cain, Kathleen / Barran, Perdita E. / de Silva, Thushan I / Sayers, Jon R

bioRxiv

Abstract: The fundamental biology of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (Ncap), its use in diagnostic assays and its potential application as a vaccine component have received considerable attention since the outbreak ...

Abstract	The fundamental biology of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (Ncap), its use in diagnostic assays and its potential application as a vaccine component have received considerable attention since the outbreak of the Covid19 pandemic in late 2019. Here we report the scalable expression and purification of soluble, immunologically active, SARS-CoV-2 Ncap in Escherichia coli. Codon-optimised synthetic genes encoding the original Ncap sequence and four common variants with an N-terminal 6His affinity tag (sequence MHHHHHHG) were cloned into an inducible expression vector carrying a regulated bacteriophage T5 synthetic promoter controlled by lac operator binding sites. The constructs were used to express Ncap proteins and protocols developed which allow efficient production of purified Ncap with yields of over 200 mg per litre of culture media. These proteins were deployed in ELISA assays to allow comparison of their responses to human sera. Our results suggest that there was no detectable difference between the 6His-tagged and untagged original Ncap proteins but there may be a slight loss of sensitivity of sera to other Ncap isolates.
Keywords	covid19
Language	English
Publishing date	2024-01-09
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.01.08.574531
Database	COVID19

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